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Effects of endothelin ET A receptor antagonism on granulocyte and lymphocyte accumulation in LPS‐induced inflammation
Author(s) -
Sampaio André L. F.,
Rae Giles A.,
Henriques Maria das Graças M. O.
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1003504
Subject(s) - biology , chemokine , eosinophil , immunology , inflammation , medicine , endocrinology , asthma
Endothelin peptides play active roles in different aspects of inflammation. This study investigates the contribution of endogenous endothelins to lipopolysaccharide (LPS) pulmonary inflammation by assessing the influence of ET A receptor antagonism on leukocyte accumulation, granulocyte adhesion molecule expression, and chemokine/cytokine modulation. Local pretreatment with BQ‐123 or A‐127722 (150 pmol), two selective and chemically unrelated endothelin ET A receptor antagonists, inhibits neutrophil and eosinophil accumulation in LPS‐induced pleurisy at 24 h but not neutrophil migration at 4 h. The effect of endothelin antagonism on neutrophil accumulation at 24 h was concomitant with inhibition of eosinophil and CD4 and CD8 T lymphocyte influx. It is surprising that the ET A receptor blockade did not inhibit the accumulation of γδ T lymphocytes, cells that are important for granulocyte recruitment in this model. Blockade of ET A receptors did not influence the expression of adhesion molecules (CD11b, CD49d) on granulocytes but abrogated the increase in tumor necrosis factor α levels 4 h after LPS stimulation and also markedly inhibited increases in levels of interleukin‐6 and keratinocyte‐derived chemokine/CXC chemokine ligand 1 but not eotaxin/chemokine ligand 11. Thus, acting via ET A receptors, endogenous endothelins play an important role in early cytokine/chemokine production and on granulocyte and lymphocyte mobilization in LPS‐induced pleurisy.